DJ-1 knock-down in astrocytes impairs astrocyte-mediated neuroprotection against rotenone.
Mutations that eliminate DJ-1 expression cause a familial form of Parkinson's disease (PD). In sporadic PD, and many other neurodegenerative diseases, reactive astrocytes over-express DJ-1 whereas neurons maintain its expression at non-disease levels. Since DJ-1 has neuroprotective properties, and since astrocytes are known to support and protect neurons, DJ-1 over-expression in reactive astrocytes may reflect an attempt by these cells to protect themselves and surrounding neurons against disease progression. We used neuron-astrocyte contact and non-contact co-cultures to show that DJ-1 knock-down in astrocytes impaired their neuroprotective capacity, relative to wild-type astrocytes, against the neurotoxin rotenone. Conversely, DJ-1 over-expression in astrocytes augmented their neuroprotective capacity. Experiments using astrocyte conditioned media on neuron-only cultures suggested that astrocyte-released, soluble factors were involved in the DJ-1-dependent, astrocyte-mediated neuroprotective mechanism. Our findings support the developing view that astrocytic dysfunction, in addition to neuronal dysfunction, may contribute to the progression of a variety of neurodegenerative disorders.
Mullett
Steven J
SJ
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Hinkle
David A
DA
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D034741:RNA, Small Interfering / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D014162:Transfection
D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D012402:Rotenone; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1